Effects of Beraprost on Intestinal Microcirculation and Barrier Function in a Mouse Model of Renal Failure.

Objective: Endothelial dysfunction plays an important role in the pathogenesis of chronic kidney disease. Prostacyclin (PGI), an endothelial cell-produced endogenous prostaglandin, plays a crucial role in maintaining endothelial function. However, its effects on intestinal microcirculation and barrier function are not fully understood.

Evaluation of glomerular hemodynamic changes by sodium-glucose-transporter 2 inhibition in type 2 diabetic rats using in vivo imaging.

The mechanisms responsible for glomerular hemodynamic regulation with sodium-glucose co-transporter 2 (SGLT2) inhibitors in kidney disease due to type 2 diabetes remain unclear. Therefore, we investigated changes in glomerular hemodynamic function using an animal model of type 2 diabetes, treated with an SGLT2 inhibitor alone or in combination with a renin-angiotensin-aldosterone system inhibitor using male Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats. Afferent and efferent arteriolar diameter and single-nephron glomerular filtration rate (SNGFR) were evaluated in ZDF rats measured at 0, 30, 60, 90, and 120 minutes after the administration of a SGLT2 inhibitor (luseogliflozin).

Comparison of emergency transport for acute alcohol intoxication before and after the coronavirus disease 2019 pandemic: A retrospective observational study.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has had a broad effect on social, economic, educational, and political systems. We investigated the effect of COVID-19 on emergency transportation due to acute alcohol intoxication in the Kochi Prefecture in Japan, a region with high alcohol consumption. This retrospective observational study was conducted using the data of 62,138 patients from the Kochi-Iryo-Net database, Kochi Prefecture's emergency medical and wide-area disaster information system.

Activation of the inflammasome drives peritoneal deterioration in a mouse model of peritoneal fibrosis.

During peritoneal dialysis (PD), the peritoneum is exposed to a bioincompatible dialysate, deteriorating the tissue and limiting the long-term effectiveness of PD. Peritoneal fibrosis is triggered by chronic inflammation induced by a variety of stimuli, including peritonitis. Exposure to PD fluid alters peritoneal macrophages phenotype.

Insights into the Regulation of GFR by the Keap1-Nrf2 Pathway.

Key Points: Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1-NF (erythroid-derived 2)–like 2 pathway increases GFR without an appreciable increase in intraglomerular pressure. Kelch-like ECH-associated protein 1-NF (erythroid-derived 2)–like 2 pathway regulates GFR through changes in filtration area by modulating calcium dynamics and contractility in glomerular cells.

Background: Literature data suggest that the activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF (erythroid-derived 2)–like 2 (Nrf2) pathway increases GFR in patients with type 2 diabetes and CKD.

Acute effect of the COVID-19 pandemic on emergency transportation due to acute alcoholic intoxication: a retrospective observational study.

Background: The COVID-19 pandemic has caused changes in people's drinking habits and the emergency management system for various diseases. However, no studies have investigated the pandemic's impact on emergency transportation for acute alcoholic intoxication. This study examines the effect of the pandemic on emergency transportation due to acute alcoholic intoxication in Kochi Prefecture, Japan, a region with high alcohol consumption.

Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation.

Chronic kidney disease is a common problem in the elderly and is associated with increased mortality. We have reported on the role of nitric oxide, which is generated from endothelial nitric oxide synthase (eNOS), in the progression of aged kidneys. To elucidate the role of endothelial dysfunction and the lack of an eNOS-NO pathway in ageing kidneys, we conducted experiments using eNOS and ASC-deficient mice.

Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia.

Serum zinc (Zn) levels tend to be low in chronic kidney disease (CKD) patients. This cohort study was conducted to investigate the relationship between zinc deficiency and CKD progression. Patients were classified into two groups based on Zn levels < 60 μg/dl (low-Zn group, n = 160) and ≥ 60 μg/dl (high-Zn group, n = 152).

Evaluation of Neutrophil Dynamics Change by Protective Effect of Tadalafil After Renal Ischemia/Reperfusion Using In Vivo Real-time Imaging.

Background: Neutrophils play a major role in ischemia/reperfusion injury (IRI) in renal transplantation and acute kidney injury. However, it has been difficult to observe changes in neutrophil dynamics over time in living mice kidney. We investigate neutrophil dynamics in IRI in living mice using novel in vivo multiphoton microscope imaging techniques and characterize the renoprotective effects of a selective phosphodiesterase 5 inhibitor, tadalafil.

Essential role and therapeutic targeting of the glomerular endothelial glycocalyx in lupus nephritis.

Lupus nephritis (LN) is a major organ complication and cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). There is an unmet medical need for developing more efficient and specific, mechanism-based therapies, which depends on improved understanding of the underlying LN pathogenesis. Here we present direct visual evidence from high-power intravital imaging of the local kidney tissue microenvironment in mouse models showing that activated memory T cells originated in immune organs and the LN-specific robust accumulation of the glomerular endothelial glycocalyx played central roles in LN development.

Klotho is a novel therapeutic target in peritoneal fibrosis via Wnt signaling inhibition.

Background: Long-term exposure to bioincompatible peritoneal dialysate causes the loss of mesothelial cells and accumulation of matrix proteins, leading to an increase in the thickness of the submesothelial layer, thereby limiting the long-term effectiveness of peritoneal dialysis (PD). However, the detailed molecular mechanisms underlying the process of peritoneal fibrosis have not been clearly elucidated. Wnt/β-catenin signaling pathway activation has been suggested to play a pivotal role in the development of organ fibrosis.

Renoprotective effects of sodium-glucose cotransporter-2 inhibitors and underlying mechanisms.

Purpose Of Review: Emerging data have demonstrated that sodium-glucose cotransporter-2 (SGLT2) inhibitors prevent cardiovascular events, especially heart failure-associated endpoints. Cardiovascular outcome trials have also suggested their renoprotective effects. One large clinical trial investigated renal primary endpoints and demonstrated that SGLT2 inhibitors slowed the progression of diabetic kidney disease (DKD).

Bardoxolone methyl analog attenuates proteinuria-induced tubular damage by modulating mitochondrial function.

Multiple clinical studies have shown that bardoxolone methyl, a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2), is effective in increasing glomerular filtration rate in patients with chronic kidney disease. However, whether an Nrf2 activator can protect tubules from proteinuria-induced tubular damage anti-inflammatory and antioxidative stress mechanisms is unknown. Using an Institute of Cancer Research-derived glomerulonephritis (ICGN) mouse model of nephrosis, we examined the effects of dihydro-CDDO-trifluoroethyl amide (dh404), a rodent-tolerable bardoxolone methyl analog, in protecting the tubulointerstitium; dh404 markedly suppressed tubular epithelial cell damage in the renal interstitium of ICGN mice.

Evaluation of Glomerular Hemodynamic Function by Empagliflozin in Diabetic Mice Using In Vivo Imaging.

Background: Sodium glucose cotransporter 2 inhibitors may reduce kidney hyperfiltration, thereby preventing diabetic kidney disease progression, which may in turn reduce cardiovascular risk, including heart failure. However, the mechanisms that regulate renal function responses to sodium glucose cotransporter 2 inhibition are not yet fully understood. We explored the renal protective effects of sodium glucose cotransporter 2 inhibition with empagliflozin, with a focus on glomerular hemodynamic effects and tubuloglomerular feedback using in vivo multiphoton microscopy imaging techniques.

The eNOS-NO pathway attenuates kidney dysfunction via suppression of inflammasome activation in aldosterone-induced renal injury model mice.

Hypertension causes vascular complications, such as stroke, cardiovascular disease, and chronic kidney disease (CKD). The relationship between endothelial dysfunction and progression of kidney disease is well known. However, the relationship between the eNOS-NO pathway and chronic inflammation, which is a common pathway for the progression of kidney disease, remains unexplored.

A single amino acid substitution in the Bombyx-specific mucin-like membrane protein causes resistance to Bombyx mori densovirus.

Bombyx mori densovirus type 1 (BmDV) is a pathogen that causes flacherie disease in the silkworm. The absolute nonsusceptibility to BmDV among certain silkworm strains is determined independently by two genes, nsd-1 and Nid-1. However, neither of these genes has been molecularly identified to date.

5-Aminolevulinic acid exerts renoprotective effect via Nrf2 activation in murine rhabdomyolysis-induced acute kidney injury.

Aim: Acute kidney injury (AKI) is associated with chronic kidney disease, as well as high mortality, but effective treatments for AKI are still lacking. A recent study reported the prevention of renal injury, such as ischemia-reperfusion injury, by 5-aminolevulinic acid (ALA), which induces an antioxidant effect. The current study aimed to investigate the effect of ALA in a rhabdomyolysis-induced mouse model of AKI created by intramuscular injection of 50% glycerol.

Infiltration of M1, but not M2, macrophages is impaired after unilateral ureter obstruction in Nrf2-deficient mice.

Chronic inflammation can be a major driver of the failure of a variety of organs, including chronic kidney disease (CKD). The NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been shown to play a pivotal role in inflammation in a mouse kidney disease model. Nuclear factor erythroid 2-related factor 2 (Nrf2), the master transcription factor for anti-oxidant responses, has also been implicated in inflammasome activation under physiological conditions.

Feasibility of fluorescence energy transfer system for imaging the renoprotective effects of aliskiren in diabetic mice.

Introduction: We investigated the feasibility of using a fluorescence resonance energy transfer system to image enzymatic activity in order to evaluate the effects of aliskiren (a direct renin inhibitor) on diabetic nephropathy.

Materials And Methods: First, we induced diabetes in C57BL/6J mice using streptozotocin, then treated them with either aliskiren (25 mg/kg/day) or the angiotensin type 1 receptor blocker valsartan (15 mg/kg/day) for four weeks. Finally, we utilized renin fluorescence resonance energy transfer substrate to assess renin activity.

Intravital imaging in the kidney.

Purpose Of Review: The review aims to provide a brief summary and evaluation of the current state of research that uses multiphoton fluorescence microscopy for intravital kidney imaging.

Recent Findings: Direct visualization of the glomerular filter, proximal and distal tubule segments, and the renal vasculature in the living, intact kidney in zebrafish, mouse, and rat models with high temporal and spatial resolution provided new insights into the function of the normal and diseased kidney. New technical developments in fluorescence excitation and detection, in combination with transgenic animal models for cell function and fate mapping, and serial imaging of the same glomerulus in the same animal over several days further advanced the field of nephrology research, and the understanding of disease mechanisms.

Activation of endothelial NAD(P)H oxidase accelerates early glomerular injury in diabetic mice.

Increased generation of reactive oxygen species (ROS) is a common denominative pathogenic mechanism underlying vascular and renal complications in diabetes mellitus. Endothelial NAD(P)H oxidase is a major source of vascular ROS, and it has an important role in endothelial dysfunction. We hypothesized that activation of endothelial NAD(P)H oxidase initiates and worsens the progression of diabetic nephropathy, particularly in the development of albuminuria.

Novel in vivo techniques to visualize kidney anatomy and function.

Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution, which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment.